We propose a two center, randomized controlled trial evaluating the efficacy and cost-effectiveness of computer-assisted cognitive-behavior therapy (CCBT) for outpatients with major depressive disorder (MDD). Results of a preliminary study indicated that, despite reducing the amount of therapist contact by about 50%, CCBT was at least as effective as an 8 week course of conventional individual CBT on depression outcomes, with greater effects on dysfunctional attitudes and knowledge about CBT. We now propose to conduct a more rigorous test of the therapeutic equivalence and cost-effectiveness of CCBT versus a full 16 week, 20 session course of individual CBT, which provides three times the amount of therapeutic contact. A total of 172 male and female outpatients (86 per site) meeting SCID/DSM-IV criteria for MDD will be randomized across five years. Outcomes will be assessed by independent evaluators without knowledge of the treatment received. The study is designed to have the statistical power to test the equivalence of CCBT and the full course of CBT at both the end of acute phase therapy and across 6 months of follow-up. In addition to effects on depressive symptoms and categorical outcomes (i.e., response and remission rates), dependent variables will include measures of dysfunctional attitudes, social functioning, quality of life, and health care costs and utilization. It is predicted that: 1) CCBT will be equivalent to CBT at week 16 and across the 6 month follow-up; and 2) CCBT will be significantly more cost-effective than CBT. Secondary aims include testing potential moderators of treatment outcome and the predicted absence of site differences (as an indicator of disseminability). This trial has significant implications for the public health because it will provide a rigorous test the clinical utility of CCBT against a model of conventional individual therapy that offers three times as much clinical contact. If equivalence and cost- effectiveness are demonstrated, the proposed research will set the stage for larger scale studies evaluating broader dissemination of CCBT. PUBLIC HEALTH RELEVANCE: Although Cognitive Behavior Therapy (CBT) is an effective treatment for major depressive disorder, its utility is limited by cost and availability of trained therapists. Computer-assisted delivery of this therapy (CCBT) has shown promise and may offer similar benefits as CBT with as little as one third the amount of therapist time. The proposed study will test the therapeutic equivalence and cost-effectiveness of CCBT versus CBT across a 16 week acute phase and a 6 month follow-up.